1. Field of Invention
The present invention is related to retrograde perfusion, in particular in connection with cardiopulmonary bypass, and more particularly including a dedicated retrograde cerebral perfusion apparatus with systems and apparatus to monitor and enhance the flow of blood across the brain.
2. Description of the Prior Art
Cardiopulmonary Bypass (CPB)
Cardiopulmonary bypass (CPB) enables patients to undergo cardiac or "open-heart" surgery. CPB is also termed "extracorporeal circulation" (ECC), or the "heart-lung machine." As the name implies, CPB performs the function of the heart (pumping blood) and lungs (oxygenating blood). During cardiac or open heart surgery, surgeons often need to arrest the contractile function of the heart in order to operate. During this phase, the function of the heart and lungs are taken over by a heart-lung machine, known as cardiopulmonary bypass.
There are several different arrangements for cardiopulmonary bypass, each having certain basic components. Blood is drained from the venous section (right) of the heart via a single cannula in the right atrium (atrial) or via two cannula placed in the superior and inferior vena cava (bicaval). If cannula cannot be placed for technical or anatomic reasons, the venous drainage may be accomplished via a cannula in the femoral vein (groin region). An arterial cannula is placed in the aorta and returns oxygenated blood back to the patient. This cannula usually enters the aorta above the aortic valve.
If the aorta is diseased such as by the presence of an aneurysm, the arterial line may be placed in the femoral or iliac artery instead of the aorta. Instead of a bicaval venous line, the femoral vein may be used for venous return. These arrangements are commonly termed "femoral-femoral bypass", "bicaval-femoral bypass", or "atrio-femoral" bypass.
In a simple CPB system, blood flows from a venous line through an extracorporeal circuit where it is oxygenated and pumped back to the body of the patient through an arterial line. The pump serves as the mechanism for drawing blood from the right side of the heart through the various other components of the CPB system and back to the patient via the arterial component described below. Two types of extracorporeal pumps are available, peristaltic or roller pumps, and centrifugal pumps. Peristaltic pumps compress tubing creating movement of blood. Centrifugal pumps have spinning fins that create movement of blood within tubing. Because roller pumps are more traumatic to blood elements, centrifugal pumps are often preferred.
The oxygenator adds oxygen to blood and enables removal of carbon dioxide. Blood flows through the oxygenator back to the patient. In bubble oxygenators, oxygen is bubbled through the blood, whereas in membrane oxygenators, blood is oxygenated through contact with an elaborate system of membranes or silicone fibers. Generally, membrane oxygenators are superior to bubble oxygenators and have become the standard during open-heart surgery. Oxygenators must have a gas supply in conjunction with other components including an oxygen analyzer and flow-meter. The type of oxygenator used determines the arrangement of various CPB components. When bubble oxygenators are used, the pump is typically in-line after the oxygenator. Conversely, when membrane oxygenators are used, a blood reservoir precedes the in-line pump which precedes the heat exchanger/oxygenator ensemble. This arrangement is suited to the retrograde cerebral perfusion system discussed below.
The function of the heat exchanger is to add or remove heat from blood in order to control body temperature. As described below, during cardiac surgery, surgeons may elect to cool the patient. Heat exchangers typically have a large metal surface which creates a boundary between the blood and water circulating through the heat exchanger. Because of a temperature difference between of the water and the blood, a heat transfer process permits heating or cooling of the blood.
The venous reservoir serves as a back up system for the CPB circuit. Since flows of four to five liters/minute may be needed for a large adult male, a reservoir of blood is needed to ensure that air is not pumped back to the patient. The reservoir serves as a depot of blood volume for the CPB circuit. In addition, a cardiotomy reservoir may be incorporated into the CPB circuit for collection of air and debris. The cardiotomy reservoir collects blood recovered from the surgical field or via venting. Cardiotomy blood may be quite denatured, requiring special defoamers and filters to remove clots, other large particulate debris and microemboli. In addition, several filters may be incorporated into the CPB circuit for collection of air and debris.
Various techniques are used to arrest the heart using special solutions known collectively as cardioplegia. Cardioplegia usually comprises a solution that arrests the heart so that it is not contracting during surgery and contains materials capable of protecting the heart muscle from ischemic injury during the period of arrest. Cardioplegia contains high concentrations of potassium, and may have either a blood (sanguinous) or crystalloid (asanguinous) basis. Cardioplegia may be administered either antegrade (the cardioplegia solution is passed via the aortic root into the coronary arteries) or retrograde (the flow of cardioplegia is directed via the coronary sinus and veins backwards into the coronary arteries) and may be either warmed or cooled. Retrograde cardioplegia systems, so named because the venous component of the heart is directly perfused, have their own blood reservoirs, heating circuits, and pumping mechanisms which may or may not incorporate oxygenated blood. Retrograde cardioplegia is completely different from retrograde cerebral perfusion. Retrograde cardioplegia delivery has also been termed "retroperfusion." Retroperfusion in this context refers to perfusion of the cardiac muscle itself through retrograde flow. The term "retrograde perfusion" in the context of this application refers to the pumping of oxygenated fluids in a retrograde direction into the venous vessels with or without collection of deoxygenated fluids from arterial vessels. "Retrograde cerebral perfusion" pertains to a subset of retrograde perfusion in which the brain is perfused in a direction retrograde to the direction of normal blood flow. The term "fluids" in the context of this application refers to blood, synthetic fluids, or mixtures of the two.
Systems for direct perfusion of the heart without open-chest surgical procedures have been developed for acute treatment of heart attacks using extracorporeal circulation via the femoral arteries. Such a system, as described in U.S. Pat. No. 5,011,469, is directed towards treating damaged myocardium rather than preventing or minimizing damage to the brain as is the subject of the present invention.
Theoretically, some systems designed for controlled delivery of fluids during surgery could be adapted for pumping oxygenated fluid mixtures through the brain. Thus, International Application PCT/US95/02694 is directed towards a pressure control system for delivery of cardioplegia and other blood mixtures to the heart at defined constant pressure, but suggests that the system may be adapted for use in the controlled perfusion of other isolated structures such as a limb or the brain. The reference describes the use of control panels and visual displays to provide information on pressure within the relevant aspects of the perfusion system together with pressure control and pumping means. PCT/US95/02694 does not describe the use of a pediatric scaled retrograde perfusion apparatus for use in adults. Further, PCT/US95/02694 does not contemplate or provide a solution for the special problem of internal jugular vein valve impedance encountered during retrograde perfusion of the brain that is a subject of the present invention.
Hypothermic CPB and Profound Hypothermic Circulatory Arrest
As mentioned above, during cardiopulmonary bypass, the patient's body may be cooled to 24.degree. C. This is known as hypothermic cardiopulmonary bypass. Lowering the body temperature provides protection to certain organs such as the brain. However, some surgeons do not cool the body during CPB and proceed with normothermic CPB. Alternatively, surgeons may use a combination of techniques such as cooling of the heart but not the body.
Certain forms of cardiac surgery use hypothermic cardiopulmonary bypass in connection with another modality. With aneurysms of the aortic arch, for example, cardiopulmonary bypass is used with either Profound Hypothermic Circulatory Arrest (PHCA) (cooling to 14-19.degree. C.) or deep hypothermic circulatory arrest (cooling to 20-25.degree. C). The cardiopulmonary pump is then switched off so that all circulatory function ceases. During PHCA, the surgeon repairs the aneurysm as quickly as possible so that hypothermic cardiopulmonary bypass and perfusion of the brain and other vital organs may recommence. Once cardiopulmonary bypass has restarted, the patient is gradually warmed to normal body temperature, until such time as cardiopulmonary bypass may be withdrawn and normal myocardial function resumed.
PHCA should not last longer than forty-five to sixty (45-60) minutes which is considered to be the safe limit for PHCA because irreversible brain damage may ensue even at low temperatures. After about sixty minutes, the incidence of cerebrovascular accidents such as stroke increases dramatically. In spite of this risk, the time required to effect repair may exceed the 45-60 minute window of relative safety.
Cerebral Perfusion
The time limitation associated with PHCA has led researchers and clinicians to explore other techniques or at least modifications or improvements of existing techniques that will prevent damage to the brain during periods of prolonged oxygen deprivation. One such technique is called "selective/antegrade perfusion" of the cerebral vasculature. In this technique, the surgeon places additional cannula in the innominate (brachiocephalic), left common carotid, or left subclavian arteries in order to permit selective perfusion of the brain using the normal direction of vascular flow. Continuous cooling and administration of neuroprotective agents during PHCA may be additional advantages. Selective/antegrade perfusion may also be used in conjunction with systemic perfusion via the femoral artery during PHCA, with or without clamping the distal aorta (referred to as the open anastomosis technique).
Although selective/antegrade perfusion affords significant brain protection during PHCA, and is clearly better than PHCA alone from the standpoint of cerebral oxygenation, selective/antegrade perfusion is technically very cumbersome and may interfere with the surgical approach or prolong the duration of PHCA. More significantly, placement of the cannula in the carotid arteries may damage friable vessels and dislodge atheromatous material into the cerebral circulation and has been associated with a high stroke incidence. Svensson et al., J. Thorac. Cardiovasc. Surg. 106:19-31 (1993). Indeed, notwithstanding effective cerebral circulatory support provided by antegrade perfusion, the incidence of survival using antegrade perfusion is not significantly improved over no perfusion at all because of the dramatic increase in deaths due to stroke. Kitamura et al., Ann. Thorac. Surg. 59: 1195-1199 (1995).
Retrograde Cerebral Perfusion
Another technique used during PHCA is called retrograde cerebral perfusion (RCP). Like selective/antegrade perfusion, the brain is perfused during RCP but in an opposite direction to normal perfusion, i.e. via the internal jugular veins. Retrograde cerebral perfusion was first used to prevent or control the incidence of air embolism during cardiac surgery. Mills and Ochsner, J. Thorac. Cardiovasc. Surg. 80:708-717 (1980). Subsequently, intermittent RCP was used for the purpose of providing protection to the brain during PHCA. Lemole et al., J. Thorac. Cardiovasc. Surg. 83:249-255 (1982). Later, continuous retrograde cerebral perfusion was developed after surgeons noted the appearance of dark, deoxygenated blood at the aortic arch suggesting perfusion of the brain in the opposite or retrograde direction to normal circulation. Ueda et al., J. Cardiovasc. Surg. 31:553-558 (1990).
During continuous RCP, blood is forced to flow in the opposite direction up the internal jugular vein to the brain. If blood traveled unimpeded up this path, it would be expected to perfuse the brain, travel down the carotid arteries and be ultimately recovered at the aortic arch. The appearance of dark, deoxygenated blood at the aortic arch suggests that perfusion does in fact occur and that brain metabolism is supported although in an opposite direction to that which occurs during normal circulatory function. Ueda et al., J. Card. Surg. 9: 584-595 (1994). Moreover, canine research suggests that retrograde cerebral perfusion provides nutritional substrates to the brain during PHCA and washes acid metabolites out of the brain. Usui et al., Ann. Thorac. Surg. 53: 47-53 (1992).
Research has also shown that retrograde cerebral perfusion is effective in augmenting the brain protection provided by PHCA. By providing perfusion of the brain, retrograde cerebral perfusion has the potential to increase the safe duration of PHCA. In a recent study using hypothermic circulatory arrest alone, 3/3 patients whose surgeries exceeded 60 minutes never regained consciousness after surgery. In contrast, when RCP was used, all 16 patients whose surgery exceeded 60 minutes regained consciousness without evidence of overt neurologic sequelae. Deeb et al., J. Thorac. & Cardiovasc. Surg. 109: 259-268 (1995). Importantly, as compared with antegrade cerebral perfusion, retrograde cerebral perfusion has been found to be significantly easier to perform, is less demanding of the surgeon's time, requires less equipment in the surgical field, and avoids the risk of damage to vital arteries supplying the brain. Yasuura et al., Ann. Thorac. Surg. 53: 655-658 (1992).
While RCP holds out the promise of protecting the brain from the devastating effects of anoxia during prolonged surgery, several problems remain. It is uncertain in each individual patient whether effective blood flow to the brain is occurring because valves may be located in the internal jugular vein which may partially or completely impede flow of oxygenated blood or pharmacologic agents to the brain. Cerebral death, thought to be due to such blockage, has been reported. Tsuchida et al., Cardiovasc. Surg. 1: 701-703 (1993).
Studies have provided estimates that in over 80% of the human population, single, bicuspid or tricuspid valves exist within both internal jugular veins (IJV) approximately one inch distal (toward the head) to the junction of the IJV with the brachiocephalic/subclavian vein. These valves are thought to be vestigial remnants of a valvular system required to maintain intracranial pressure when walking in a semi-horizontal position. Conversely, in some patients, the valves may be nonexistent or poorly developed. While IJV valves are apparently not necessary, they are thought to function in limiting transmission of excessive increases in venous pressure to the brain during coughing, straining or Vasalva maneuvers. Studies have shown competence of these valves against pressure, such as during straining or coughing while controlled studies in cadavers have examined competence of these valves against pressure to retrograde flow at various pressures. In approximately 10 to 15 percent of patients, IJV valves may resist pressures as high as 75 mm Hg. Further, the competence of these valves may be influenced by monitoring lines which are placed during surgery in the internal jugular veins and resulting in reduced valve impedance.
Retrograde cerebral perfusion is currently performed by selective clamping of cannula in place for use with the cardiopulmonary bypass machine. By selective clamping of the arterial and venous lines and through use of cannula placed in the large arterial and venous vessels entering and leaving the heart, blood may be directed in a retrograde direction up the superior vena cava and the internal jugular veins by the action of the cardiopulmonary bypass pump. Numerous examples exist in the medical literature which describe the use of routine cardiopulmonary bypass equipment to drive retrograde cerebral perfusion. Examples and descriptions of the current practice of effective retrograde perfusion by selective clamping of arterial and venous lines running to the cardiopulmonary bypass machine can be seen in McLoughlin, et al., "Continuous Retrograde Cerebral Perfusion as an Adjunct to Brain Protection During Deep Hypothermic Systemic Circulatory Arrest", J. Cardiothorac. & Vasc. Anest. 9: 205-214 (1995); Murase et al., "Continuous Retrograde Cerebral Perfusion for Profusion of the Brain during Aortic Arch Surgery", Eur. J. Cardiothorac. Surg. 7:597-600 (1993); Raskin and Coselli, "Retrograde Cerebral Perfusion: Overview, Techniques and Results", Perfusion 10: 51-57 (1995); and Ueda et al., "Protective Effect of Continuous Retrograde Cerebral Perfusion on the Brain During Deep Hypothermic Systemic Circulatory Arrest", J. Card. Surg. 9: 584-595 (1994).
A synchronized gas operated balloon catheter inflation apparatus for effecting retrograde perfusion of the heart and other organs is the subject of U.S. Pat. No. 5,011,468. This reference is directed towards a retrograde perfusion and retroinfusion control apparatus that inflates and deflates balloon catheters to occlude and redirect blood flow in synchrony with the normal cardiac cycle. While the reference primarily describes the operation of a balloon catheter pumping means synchronized to electrocardiographic signals dedicated to the retrograde perfusion of the heart, it includes the possibility of using a modified system for selective retrograde perfusion of the brain by diverting balloon catheters branching from the primary cardiac oxygenation loop for retrograde perfusion of the brain. The system described in 5,011,468, if modified for cerebral retrograde perfusion, would avoid the problem of blood flow impedance caused by valves within vessels leading to the brain by placement of balloon catheters in a supravalvular position distal to the internal jugular vein valves. Thus, this reference is directed to a perfusion system that is fundamentally different from that used in the present invention.
U.S. Pat. No. 4,686,085 and related patents issued to Osterholm describe systems that deliver specialized solutions into the cerebrospinal fluid pathways for selective perfusion of the brain for treatment of ischemic incidents (stroke). The Osterholm references are completely different in methodology and purpose from the present invention because they describe perfusion through the ventriculo-cisternal spaces occupied by cerebral spinal fluid rather than the blood vasculature of the brain. The purpose of the Osterholm inventions is to minimize the effects of stroke rather to prevent damage to the brain during cardiovascular surgery as is the subject of the present invention.
Blood flow to the brain during retrograde cerebral perfusion, may be effected by using either selective or non-selective flow cannula. Selective flow cannulation is accomplished by placement of a cannula within the internal jugular vein. Non-selective flow cannulation describes an inflow system via the right atrium or the superior vena cava. Placement of the cannula in selective flow cannulation may be either infra or supravalvular. Infravalvular inflow means the retrograde cerebral perfusion flow is delivered below the internal jugular vein valves. Supravalvular inflow describes flow delivery above internal jugular vein valves thus solving problems of potential impedance produced by valves within the internal jugular veins. While this placement obviates concerns about valvular flow impedance, this procedure is often technically impracticable because it requires placement of occlusive cannula high in the cervical region. Furthermore, anesthesiologists routinely place catheters in the internal jugular vein to monitor central venous pressure, which may interfere with cannula placement using the selective method. Thus, while supravalvular selective flow systems solve the problems of possible flow impedance with the internal jugular vein valves, they involve significant difficulties in achieving the placement of the cannula and may damage the internal jugular vein valves.
RCP effected using a non-selective infravalvular system avoids problems with cannula placement and is a subject of the present invention. The present invention describes an apparatus in which inflow conduits, typically employing cannula, are placed infravalvular, or on the heart side, of the internal jugular vein valves. This placement is herein described as "proximal" to the location of the internal jugular vein valves. Flow measurement means, such as pressure manometers, are placed in association with the inflow conduits in order to insure that desired input pressures are met but not exceeded.
The resistance to sustained flow and pressure is slightly different physiologically from that occurring with a sudden increase in pressure (such as with coughing). In the former, valves have been observed to flutter so that impedance is not complete but instead, partial. With partial obstruction, some blood flow does occur across the valves. Nonetheless, when retrograde cerebral perfusion is initiated, these valves may produce variable and unpredictable impedance to blood flow up the internal jugular veins. Valve impedance can increase the rate of shunting into collateral venous systems such as into the azygos venous system.
The azygos vein originates from the SVC prior to its bifurcation into the brachiocephalic veins. The azygos vein runs down through the thoracic and lumbar region branching extensively along the way to create the "caval-azygo-lumbar" venous system. One of these branches connects to the vertebral venous system which contributes to venous plexi of the foramen magnum which is in turn connected to the intracranial venous sinuses. Thus, the azygos system provides another potential avenue to deliver blood and pharmacologic agents to the brain.
Ultimately, the azygos vein drains into the inferior vena cava. A cadaveric study using latex infusion has indicated that, during RCP, pressure induced by valvular obstruction of the internal jugular vein forces additional blood into the azygos vein. In the face of near complete valvular obstruction, the azygos system may provide a major conduit of retrograde fluids into the central nervous system. De Brux et al., Ann. Thorac. Surg. 60:1294-1298 (1995). Animal evidence has suggested that some, if not a majority of the blood introduced in a retrograde fashion into the internal jugular vein flow is diverted into the azygos vein. From there it could flow either down into the inferior vena cava or to the brain by a route different than through the internal jugular vein. Questions still remain as to percentage of blood which is actually shunted through channels other than the cerebral vasculature. Although blood recovered from the retrograde stream appears to be deoxygenated, it is possible that the oxygen has been absorbed in tissues other than the brain, i.e. muscle bone, skin, etc.
Taken together, it is clear that variability between individuals in the resistance of the internal jugular vein valve to retrograde flow, and the associated shutting to collateral vessels, results in the observed lack of direct, predictable correlation between perfusion pressure and perfusion flow rates. For these reasons, maintenance of desired perfusion pressure at the level of the superior vena cava and even maintenance of desired flow rates therein may not provide accurate estimates of cerebral perfusion. Thus, surgery may be continued beyond the safe period of 45-60 minutes under the mistaken impression that the brain is safe from anoxic damage and it is only upon failure of attempted resuscitation after completion of the procedure that insufficient oxygenation is retrospectively discovered.
Because problems with internal jugular vein valve impedance may result in occult failure of cerebral oxygenation, effective retrograde cerebral perfusion using non-selective infravalvular flow cannulation requires improved systems for monitoring and controlling blood flow to the brain. A need exists for a dedicated system that selectively treats retrograde cerebral perfusion as an independent circulation, as opposed to the current practice of providing RCP using modifications of standard extracorporeal circuit or cardiopulmonary bypass equipment. Such a dedicated system could provide oxygenation and cooling of blood in a controlled manner as well as to provide improved and more isolated perfusion of the brain with desired pharmacologic agents.
There is a need for a system designed specifically for retrograde perfusion which is controlled independently from the cardiopulmonary bypass machine and is designed for the flow rates used during retrograde perfusion. The cardiopulmonary bypass apparatus is capable of flow rates of up to 5 liters per minute. Retrograde perfusion is typically conducted at flow rates of less than 600 milliliters per minute. The lower flow rates required by retrograde perfusion could be more effectively provided using smaller scale apparatus that is designed for lower flow rates. Equipment, including pumps, oxygenators, and heat exchangers currently available for use in pediatric surgery are better suited to retrograde perfusion. Smaller scale equipment provides for reduced prime volumes and conserves both the patient's blood, synthetic fluid mixtures and pharmacologic additives. In the context of this application, pediatric scale refers to perfusion equipment with maximum flow rates of less than 2 liters per minute. Such a dedicated system could be used not only for the retrograde perfusion of the cerebrum but could also be used if desired for perfusion of an isolated organ or organ system including the visceral organs.
There is a specific need for a system capable of determining the extent to which flow of oxygenated blood and pharmacologic agents is compromised by competent valves within the internal jugular veins. Relevant information can be acquired by concomitant monitoring of pressure both proximal and distal to the internal jugular vein valves, thus permitting estimates of the efficacy of cerebral perfusion. There is a further need for a system capable modulating pressure and thus perfusion rates within the cerebral circulation by controlling outflow via collateral circulatory pathways such as the azygos vein complex. These needs and the solution thereto form the basis of the present claimed invention.
The present invention comprises dedicated apparatus and methods for providing improved retrograde perfusion, particularly retrograde cerebral perfusion, under controlled conditions. Both the retrograde perfusion circuitry and monitoring and control apparatus are designed to be assembled from commercially available components.